Dihydroergotamine mesylate is the methanesulphonate salt of dehydrogenated ergot alkaloid. It is used for the acute treatment of migraine and cluster headache episodes. Dihydroergotamine is a serotonin receptor agonist and causes vasoconstriction of the intracranial blood vessels. Oral bioavailability of dihydroergotamine is poor and it is not available in oral form in the U.S. Dihydroergotamine is presently marketed both as a nasal spray and as an injectable product in the name of D.H.E. 45° Injection 1 mg/ml, which is supplied in sterile ampoules for intravenous, intramuscular, or subcutaneous administration.
U.S. Pat. No. 6,495,535 B1 discloses an injectable formulation of dihydroergotamine containing 1 mg/ml or 2 mg/ml of dihydroergotamine mesylate, filled in a medicament container (such as a prefilled syringe). The dihydroergotamine formulation includes dihydroergotamine or salts thereof, pharmaceutically acceptable liquid vehicle, organic solvents, antioxidants and pH-adjusting agent, with the pH of the dihydroergotamine mesylate composition at 3.6±0.2. Applicants tested the composition according to U.S. Pat. No. 6,495,535 for chemical stability and it was found that the solution, having a pH of 3.6±0.2, showed unacceptable and high amount of isomeric and oxidative impurities.
There remains a need for a stable solution of dihydroergotamine that provides minimal amount of impurities and is also presented in a self-administrable form.